Trans-splicing and split inteins
The canonical way of protein splicing, where the intein is excised from its precursor protein and the flanking fragments are ligated is also called cis-splicing. In fact, in nature inteins have been found in two separate polypeptide chains. A split intein can catalyze a protein ligation in trans, leading to two exteins from different polypeptide chains to be ligated into one chain (Hong Wu et al., 1998). Protein trans-splicing (PTS) is an important instrument in many modern applications in biotechnology, such as protein engineering (Topilina and Mills, 2014).
In trans-splicing, one precursor protein contains a N-extein and N-terminal intein fragment fused together, and the second precursor protein consists of the C-terminal intein fragment fused together with C-extein. For the precursor proteins to undergo the trans-splicing reaction, the two intein fragments must be re-associated. During the reaction, the inteins auto-catalytically self-excise, and the N-extein and C-extein are melded with a peptide bond. (Shah and Muir, 2011)